The Structural Molecular Biology program of the Fred Hutchinson Cancer Research Center seeks a major upgrade of our shared, in-house x-ray crystallography facility in order to maintain the high quality of research and level of productivity achieved over the past decade-plus of its existence. This upgrade would replace aging equipment with a state-of-the-art system (a Rigaku/MSC High-Throughput HomeLab), maximally leveraging still useful equipment in the current facility. This upgrade addresses 3 major concerns: 1) Replacement of a failing (12+ years) image plate detector (R-AXIS Me) that is soon to lose manufacturer support; 2) Dramatically expanding the capability of the current system to allow in-house experiments previously requiring use of our limited synchrotron time; 3) Increasing the in-house data collection throughput to relieve wait-times on a currently saturated facility and facilitate dramatic expansions of the individual research programs of the Major Users in the near future. The Hutchinson's Structural Molecular Biology program comprises 3 major users (Ferre-D'Amare, Stoddard, Strong) while also supporting 3 minor users (Cronk, Hockenbery, McFarland), 2 of whom are ex-Hutchinson post-docs that have started independent positions at undergraduate institutions lacking x-ray equipment. The individual research programs are diverse, but highly complementary and fully integrated, generating high-impact results in the fields of structural enzymology (Ferre-D'Amare, Cronk, Stoddard), structural molecular immunology (McFarland, Strong), ribozyme function and RNA topology (Ferre-D'Amare), intron-encoded restriction endonucleases (Stoddard), apoptosis (Hockenbery), structure-based drug design (Hockenbery, Stoddard) and pioneering the development of new methods in protein design and structure analysis (Stoddard, Strong). The program also supports a highly successful pre-and post-doctoral training program, interfacing with 4 separate graduate programs (Molecular and Cellular Biology (FHCRC/UW), Biochemistry (UW), Biomolecular Structure & Design (UW) and Immunology (UW)). The growing depth and breadth of the research and training programs increasingly require upgraded x-ray instrumentation and are necessary to prevent a crippling loss in productivity with the anticipated, eventual loss, due to an unrepairable breakdown, of 1 of our 2 image plate detectors (the unsupported R-AXIS IIc).